Human health is impacted by a variety of microbes encountered on a daily basis. In particular, contact with various microbes in the environment can lead to an illness, possibly severe or lethal, in mammals. For example, microbial contamination can lead to a variety of illnesses, including, but not limited to, food poisoning, a streptococcal infection, anthrax (cutaneous), influenza, athlete's foot, cold sores, conjunctivitis (“pink eye”), coxsackievirus (hand-foot-mouth disease), croup, diphtheria (cutaneous), ebolic hemorrhagic fever, and impetigo.
Viruses are a category of pathogens of primary concern. Viral infections are among the greatest causes of human morbidity, with an estimated 60% or more of all episodes of human illness in developed countries resulting from a viral infection. In addition, viruses infect virtually every organism in nature, with high virus infection rates occurring among birds, including fowl and migrating birds, and mammals, including humans, pets, livestock, and zoo specimens.
Viruses exhibit an extensive diversity in structure and life cycle. A detailed description of virus families, their structures, life cycles, and modes of viral infection is discussed in Fundamental Virology, 4th Ed., Eds. Knipe & Howley, Lippincott Williams & Wilkins, Philadelphia, Pa., 2001.
Simply stated, virus particles are intrinsic obligate parasites, and have evolved to transfer genetic material between cells and encode sufficient information to ensure their propagation. In a most basic form, a virus consists of a small segment of nucleic acid encased in a simple protein shell. The broadest distinction between viruses is the enveloped and nonenveloped viruses, i.e., those that do or do not contain, respectively, a lipid-bilayer membrane.
Viruses propagate only within living cells. The principal obstacle encountered by a virus is gaining entry into the cell, which is protected by a cell membrane of thickness comparable to the size of the virus. In order to penetrate a cell, a virus first must become attached to the cell surface. Much of the specificity of a virus for a certain type of cell lies in its ability to attach to the surface of that specific cell. Durable contact is important for the virus to infect the host cell, and the ability of the virus and the cell surface to interact is a property of both the virus and the host cell. The fusion of viral and host-cell membranes allows the intact viral particle, or, in certain cases, only its infectious nucleic acid to enter the cell. Therefore, in order to control a viral infection, it is important to rapidly kill a virus that contacts the skin, and ideally to provide a persistent antiviral activity on the skin, or a hard surface, in order to control viral infections.
Influenza viruses belong to the family Orthomyxovirdae. They are enveloped viruses, and the family contains five genera classified by variations in nucleoprotein antigens. The five genera are influenza A, influenza B, influenza C, thogotovirus, and isavirus.
Influenza virus A consists of a single species. Influenza A viruses are the major cause of influenza in humans, and all past pandemics have been caused by influenza A viruses. The influenza A genome consists of 10 genes encoding for different proteins. The two surface proteins are glycoproteins, i.e., hemagglutinin (HA) and neuraminidase (NA). These proteins are distributed evenly over the virion surface. It is the antigenic variation in these proteins that is used to define the subtypes of influenza A.
There are 16 different HA antigens (H1-H16) and nine different NA antigens (N1-N9). Human disease has historically been caused by three subtypes of HA, i.e., H1, H2, and H3, and two subtypes of NA, i.e., N1 and N2. Recently it has been recognized that human disease can be caused by other HA antigens (e.g., H5, H7, and H9).
All known subtypes of influenza A can be found in birds, and feral aquatic birds are the major reservoir for influenza A. Typically, the disease does not affect feral birds, but domestic chickens and turkeys are susceptible to severe and fatal influenza. Other mammals are also susceptible to influenza, and influenza A has caused disease in horses, pigs, whales, and seals. Furthermore, the range of subtypes that cause disease in additional species (e.g., cats, civets, dogs) is expanding.
Avian influenza is the term used to describe influenza A subtypes that primarily affect chickens, turkeys, guinea fowl, migratory fowl, and other avian species. Avian strains also are classified according to their disease severity. Two recognized forms are highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI). HPAI strains typically result in mortality rates of 100% in flocks. The current H5N1 strain is an HPAI, however, there are other strains of H5N1 that are LPAI. Human infections have been associated with both HPAI and LPAI.
The virus strain responsible for the 1918 pandemic flu was an H1N1. This strain has been reconstructed and appears to be of avian origin. The pandemic strains of 1957-58 (H2N2) and 1968-69 (H3N2) both involved reassortment between avian and human strains. Influenza nomenclature is based on (a) host of origin (if other than human), (b) geographic origin, (c) strain number, (d) year of isolation, and (e) HA and NA type. Some examples would be: A/Hong Kong/03/68(H3N2), or A/swine/iowa/15/30(H1N1). Structurally, all influenza types are the same, and for this reason a composition and method of that can inactivate or destroy one type of influenza, also can inactivate or destroy other types of influenza regardless of the genus, subtype, or species in which they infect.
Recently, avian influenza viruses emerged as a pandemic threat to the health of humans. The threat that most concerns scientists and health authorities is the deadly H5N1 avian flu virus. The H5N1 avian flu virus has ravaged poultry stocks in Asia since 2003 and recently has spread to Europe through migratory birds. More than 160 people have died of the avian flu since 2003. However, human cases of the disease have been limited to individuals who came into direct contact with infected birds. Health authorities fear this disease will mutate into a form that spreads easily from person-to-person, which can initiate a flu pandemic that could kill millions of people. It is feared that death tolls could be on the level of the 1918-1919 Spanish flu pandemic, which is estimated to have killed between 40 million and 50 million people worldwide.
Health authorities further are warning that it is not a matter of if, but when, where, and how seriously humans will be affected by an avian flu virus. The magnitude of the threat, not just to a particular country but to individuals, warrants a massive campaign to avoid bird-to-bird transmission and to avoid or inhibit human-to-human transmission of an avian flu virus. Therefore, countries around the world have taken preventive measures against a potential outbreak of avian flu, in particular, by destroying infected birds and birds that may be infected. However, a crucial part of this entire effort is individual responsibility.
From current evidence, individuals fall victim to an avian flu virus through contact with infected birds, such as chickens, turkeys, ducks, and migratory birds, for example. To date, there is little or no evidence that an avian flu virus is spread through human-to-human transmission. However, a few isolated cases have been reported of people believed to have been infected by avian flu from a person infected with the virus. Therefore, individuals most at risk of infection are those who work on poultry farms, in poultry markets, and in poultry processing plants. Furthermore, the general population may be at risk because the avian flu virus is not killed or inactivated by freezing processed fowl. Influenza also has been shown to remain infectious on nonporous surfaces for 24 to 48 hours. Recent data from the World Health Organization Laboratory has shown that H5N1 can survive in the environment for six days at 37° C. Therefore, a potential exists for individuals to be infected with avian flu virus from processed, infected fowl.
Presently, the greatest health concern centers on a strain of avian flu virus known as H5N1, a lethal form of the avian flu virus. Although, over 100 subtypes of avian flu have been identified, avian flu types normally only infect birds, and in rare instances, pigs. H5N1 is the only strain of avian flu within the H5 subtype known to infect humans.
The first documented human infection attributed H5N1 avian influenza virus occurred in 1997 in Hong Kong. The steps the government took to cull birds and stop the spread of avian flu may well have prevented the progression of the virus to mutate to allow transmission by human-to-human contact spread. But as long as the H5N1 virus continues to circulate in birds, opportunities exist for this virus to adapt and infect to humans.
Therefore, avian flu virus contamination of skin and environmental surfaces should be minimized to reduce the risk of transmitting the infection to the general population. The risk of transmitting such avian flu viral infections, and all other influenza infections, can be reduced significantly by inactivating or removing the viruses from the hands, other animate surfaces, and inanimate surfaces.
It is known that washing body parts (e.g., hand washing) and hard surfaces (e.g., countertops and sinks) can significantly decrease the population of microorganisms, including pathogens. Therefore, cleaning skin and other animate and inanimate surfaces to reduce microbial populations is a first defense in removing such pathogens from these surfaces, and thereby minimizing the risk of infection.
Common household phenol/alcohol disinfectants are effective in disinfecting contaminated environmental surfaces, but lack persistent virucidal activity. Hand washing is highly effective in disinfecting contaminated fingers, but again suffers from a lack of persistent activity. These shortcomings illustrate the need for improved virucidal compositions having a persistent activity against viruses, such as influenza viruses, including avian flu viruses.
Antimicrobial personal care compositions are known in the art. In particular, antibacterial cleansing compositions, which typically are used to cleanse the skin and destroy bacteria present on the skin, especially the hands, arms, and face of the user, are well-known commercial products.
Antibacterial compositions are used, for example, in the health care industry, food service industry, meat and fowl processing industries, and in the private sector by individual consumers. The widespread use of antibacterial compositions indicates the importance consumers place on controlling bacteria populations on skin. The paradigm for antibacterial compositions is to provide a substantial and broad spectrum reduction in bacterial populations quickly and without adverse side effects associated with toxicity and skin irritation. Such antibacterial compositions are disclosed in U.S. Pat. Nos. 6,107,261 and 6,136,771, each incorporated herein by reference.
One class of antibacterial personal care compositions is the hand sanitizers. This class of compositions is used primarily by medical personnel to disinfect the hands and fingers. A hand sanitizer is applied to, and rubbed into, the hands and fingers, and the composition is allowed to evaporate from the skin.
Hand sanitizers contain a high percentage of an alcohol, like ethanol. At the high percent of alcohol present in the gel, the alcohol itself acts as a disinfectant. In addition, the alcohol quickly evaporates to obviate wiping or rinsing skin treated with the sanitizer gel. Hand sanitizers containing a high percentage of an alcohol, i.e., about 40% or greater by weight of the composition, do not provide a persistent microbial kill.
Antibacterial cleansing compositions typically contain an active antibacterial agent, a surfactant, and various other ingredients, for example, dyes, fragrances, pH adjusters, thickeners, skin conditioners, and the like, in an aqueous and/or alcoholic carrier. Several different classes of antibacterial agents have been used in antibacterial cleansing compositions. Examples of antibacterial agents include a bisguanidine (e.g., chlorhexidine digluconate), diphenyl compounds, benzyl alcohols, trihalocarbanilides, quaternary ammonium compounds, ethoxylated phenols, and phenolic compounds, such as halo-substituted phenolic compounds, like PCMX (i.e., p-chloro-m-xylenol) and triclosan (i.e., 2,4,4′-trichloro-2′-hydroxy-diphenylether). Antimicrobial compositions based on such antibacterial agents exhibit a wide range of antibacterial activity, ranging from low to high, depending on the microorganism to be controlled and the particular antibacterial composition. Most commercial antibacterial compositions generally offer a low to moderate antibacterial activity, and no reported antiviral activity.
Antimicrobial activity is assessed against a broad spectrum of microorganisms, including Gram positive and Gram negative microorganisms. The log reduction, or alternatively the percent reduction, in microbial populations provided by the antimicrobial composition correlates to antimicrobial efficacy. A 1-3 log reduction is preferred, a log reduction of 3-5 is most preferred, whereas a log reduction of less than 1 is least preferred, for a particular contact time, generally ranging from 15 seconds to 5 minutes. Thus, a highly preferred antimicrobial composition exhibits a 3-5 log reduction against a broad spectrum of microorganisms in a short contact time.
Virus control poses a more difficult problem than bacterial control. By sufficiently reducing bacterial populations, the risk of bacterial infection is reduced to acceptable levels. Therefore, a rapid antibacterial kill is desired. With respect to viruses, however, not only is a rapid kill desired, but a persistent antiviral activity also is required. This difference is because merely reducing a virus population is insufficient to reduce infection. In theory, a single virus can cause infection. Therefore, an essentially total, and persistent, antiviral activity is required, or at least desired, for an effective antiviral cleansing composition.
WO 98/01110 discloses compositions comprising triclosan, surfactants, solvents, chelating agents, thickeners, buffering agents, and water. WO 98/01110 is directed to reducing skin irritation by employing a reduced amount of surfactant.
U.S. Pat. No. 5,635,462 discloses compositions comprising PCMX and selected surfactants. The compositions disclosed therein are devoid of anionic surfactants and nonionic surfactants.
EP 0 505 935 discloses compositions containing PCMX in combination with nonionic and anionic surfactants, particularly nonionic block copolymer surfactants.
WO 95/32705 discloses a mild surfactant combination that can be combined with antibacterial compounds, like triclosan.
WO 95/09605 discloses antibacterial compositions containing anionic surfactants and alkylpolyglycoside surfactants.
WO 98/55096 discloses antimicrobial wipes having a porous sheet impregnated with an antibacterial composition containing an active antimicrobial agent, an anionic surfactant, an acid, and water, wherein the composition has a pH of about 3.0 to about 6.0.
N. A. Allawala et al., J. Amer. Pharm. Assoc.—Sci. Ed., Vol. XLII, no. 5, pp. 267-275 (1953) discusses the antibacterial activity of active antibacterial agents in combination with surfactants.
A. G. Mitchell, J. Pharm. Pharmacol., Vol. 16, pp. 533-537 (1964) discloses compositions containing PCMX and a nonionic surfactant that exhibit antibacterial activity.
U.S. Pat. No. 6,110,908 discloses a topical antiseptic containing a C2-3 alcohol, a free fatty acid, and zinc pyrithione.
U.S. Pat. No. 5,776,430 discloses a topical antimicrobial cleaner containing chlorhexidine and an alcohol. The compositions contain about 50% to 60%, by weight, denatured alcohol and about 0.65% to 0.85%, by weight, chlorhexidine. The composition is applied to the skin, scrubbed into the skin, then rinsed from the skin.
European Patent Application 0 604 848 discloses a gel-type hand disinfectant containing an antimicrobial agent, 40% to 90% by weight of an alcohol, and a polymer and a thickening agent in a combined weight of not more than 3% by weight. The gel is rubbed into the hands and allowed to evaporate to provide disinfected hands. The disclosed compositions often do not provide immediate sanitization and do not provide persistent antimicrobial efficacy.
In general, hand sanitizer gels typically contain: (a) at least 60% by weight ethanol or a combination of lower alcohols, such as ethanol and isopropanol, (b) water, (c) a gelling polymer, such as a crosslinked polyacrylate material, and (d) other ingredients, such as skin conditioners, fragrances, and the like. Hand sanitizer gels are used by consumers to effectively sanitize the hands, without, or after, washing with soap and water, by rubbing the hand sanitizer gel on the surface of the hands. Current commercial hand sanitizer gels rely on high levels of alcohol for disinfection and evaporation, and thus suffer from disadvantages. Specifically, because of the volatility of ethanol, the primary antimicrobial agent does not remain on the skin after use, thus failing to provide a persistent antimicrobial effect.
At alcohol concentrations below 60%, ethanol is not recognized as an antiseptic. Thus, in compositions containing less than 60% alcohol, an additional antimicrobial compound is present to provide antimicrobial activity. Prior disclosures, however, have not addressed the issue of which composition ingredient in such an antimicrobial composition provides microbe control. Therefore, for formulations containing a reduced alcohol concentration, the selection of an antimicrobial agent that provides both a rapid antimicrobial effect and a persistent antimicrobial benefit is difficult.
U.S. Pat. Nos. 6,107,261 and 6,136,771 disclose highly effective antibacterial compositions containing a phenolic antimicrobial agent. These patents disclose compositions that solve the problem of controlling bacteria on skin and hard surfaces, but are silent with respect to controlling viruses.
U.S. Pat. Nos. 5,968,539; 6,106,851; and 6,113,933 disclose antibacterial compositions having a pH of about 3 to about 6. The compositions contain an antibacterial agent, an anionic surfactant, and a proton donor.
Antiviral compositions disclosed as inactivating or destroying pathogenic viruses, including rhinovirus, rotavirus, influenza virus, parainfluenza virus, respiratory syncytial virus, and Norwalk virus, also are known. For example, U.S. Pat. No. 4,767,788 discloses the use of glutaric acid to inactivate or destroy viruses. U.S. Pat. No. 4,975,217 discloses compositions containing an organic acid and an anionic surfactant, for formulation as a soap or lotion, to control viruses. U.S. Patent Publication 2002/0098159 discloses the use of a proton donating agent and a surfactant, including an antibacterial surfactant, to effect antiviral and antibacterial properties.
U.S. Pat. No. 6,034,133 discloses a virucidal hand lotion containing malic acid, citric acid, and a C1-6 alcohol. U.S. Pat. No. 6,294,186 discloses combinations of a benzoic acid analog, such as salicyclic acid, and selected metal salts as being effective against viruses, including rhinovirus. U.S. Pat. No. 6,436,885 discloses a combination of known antibacterial agents with 2-pyrrolidone-5-carboxylic acid, at a pH of 2 to 5.5, to provide antibacterial and antiviral properties.
Organic acids in personal washing compositions also have been disclosed. For example, WO 97/46218 and WO 96/06152 disclose the use of organic acids or salts, hydrotropes, triclosan, and hydric solvents in a surfactant base for antimicrobial cleansing compositions. These publications are silent with respect to antiviral properties.
Hayden et al., Antimicrobial Agents and Chemotherapy, 26:928-929 (1984), discloses interrupting the hand-to-hand transmission of rhinovirus colds through the use of a hand lotion having residual virucidal activity. The hand lotions, containing 2% glutaric acid, were more effective than a placebo in inactivating certain types of rhinovirus. However, the publication discloses that the glutaric acid-containing lotions were not effective against a wide spectrum of rhinovirus serotypes.
A virucidal tissue designed for use by persons infected with the common cold, and including citric acid, malic acid, and sodium lauryl sulfate, is known. Hayden et al., Journal of Infectious Diseases, 152:493-497 (1985), however, reported that use of paper tissues, either treated with virus-killing substances or untreated, can interrupt the hand-to-hand transmission of viruses. Hence, no distinct advantage in preventing the spread of rhinovirus colds can be attributed to the compositions incorporated into the virucidal tissues.
An efficacious antimicrobial composition effective against influenza viruses in general, and avian flu viruses in particular, is needed in the art. Such a composition would be effective in stemming the transmission of influenza viruses, and particularly highly pathogenic avian flu viruses from a contaminated source, like a bird, to a human when the infected, or potentially infected, human regularly uses the composition during or after contacting, processing, or working with the virus-contaminated source, such as fowl. Protectable humans, for example, include persons who work on poultry farms and in poultry processing plants. In the case an avian flu virus mutates and enables human-to-human contamination, such a product would be needed to inhibit the transmission of the avian flu virus throughout the population.
Although a number of antimicrobial cleansing products currently exist, taking a variety of product forms (e.g., deodorant soaps, hard surface cleaners, and surgical disinfectants), such antimicrobial products typically incorporate antimicrobial agents, e.g., a phenolic compound, and/or harsh surfactants, which can dry out and irritate skin tissues. Ideally, personal cleansing products gently cleanse the skin, cause little or no irritation, and do not leave the skin overly dry after frequent use.
Accordingly, a need exists for an antimicrobial composition that is highly efficacious against influenza viruses, and particularly avian flu viruses, in a short time period, and wherein the composition can provide a persistent antiviral activity and is mild to the skin. Personal care products demonstrating improved mildness and a heightened level of influenza virus reduction are provided by the antimicrobial compositions of the present invention.